The UDP-Glucose Receptor P2RY14 Triggers Innate Mucosal Immunity in the Female Reproductive Tract by Inducing IL-8

Arase, Toru; Uchida, Hiroshi; Kajitani, Takashi; Ono, Masanori; Tamaki, Kunihiko; Oda, Hideyuki; Nishikawa, Sayaka; Kagami, Maki; Nagashima, Takashi; Masuda, H.; Asada, Hironori; Yoshimura, Yasunori; Maruyama, Tetsuo

doi:10.4049/jimmunol.0900001

Cited by 77 publications

(101 citation statements)

References 55 publications

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“…Our data indicating that PPTN decreased mKC levels in the βENaC-Tg mouse BAL (Fig. 5) could reflect a contribution of P2Y 14 R-promoted cytokine release from alveolar epithelial cells, upstream of neutrophil recruitment [47]. In addition to the above-discussed scenario, published gene expression analyses indicated high levels of P2Y 14 R mRNA in murine alveolar macrophages [48].…”

Section: Discussionmentioning

confidence: 57%

UDP-glucose promotes neutrophil recruitment in the lung

Sesma

Weitzer

Livraghi‐Butrico

et al. 2016

Purinergic Signalling

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In addition to their role in glycosylation reactions, UDP-sugars are released from cells and activate widely distributed cell surface P2Y 14 receptors (P2Y 14 R). However, the physiological/pathophysiological consequences of UDPsugar release are incompletely defined. Here, we report that UDP-glucose levels are abnormally elevated in lung secretions from patients with cystic fibrosis (CF) as well as in a mouse model of CF-like disease, the βENaC transgenic (Tg) mouse. Instillation of UDP-glucose into wild-type mouse tracheas resulted in enhanced neutrophil lung recruitment, and this effect was nearly abolished when UDP-glucose was coinstilled with the P2Y 14 R antagonist PPTN [4-(piperidin-4-yl)-phenyl)-7-(4-(trifluoromethyl)-phenyl-2-naphthoic acid]. Importantly, administration of PPTN to βENaC-Tg mice reduced neutrophil lung inflammation. These results suggest that UDP-glucose released into the airways acts as a local mediator of neutrophil inflammation.

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Section: Discussionmentioning

confidence: 57%

UDP-glucose promotes neutrophil recruitment in the lung

Sesma

Weitzer

Livraghi‐Butrico

et al. 2016

Purinergic Signalling

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“…In particular, the uridine diphos-phate-glucose/P2RY14 (UDP-Glc/P2RY14) signaling axis has been shown to be involved in the stress response, such as inflammation and/or mechanical stress (22,23). In addition, UDP-Glc expression was detected at high levels in tumor cells (24), suggesting that it may act as a danger signal for inflammation or tumors.…”

Section: Introductionmentioning

confidence: 99%

The nucleotide sugar UDP-glucose mobilizes long-term repopulating primitive hematopoietic cells

Kook¹,

Cho²,

Lee³

et al. 2013

J. Clin. Invest.

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Hematopoietic stem progenitor cells (HSPCs) are present in very small numbers in the circulating blood in steady-state conditions. In response to stress or injury, HSPCs are primed to migrate out of their niche to peripheral blood. Mobilized HSPCs are now commonly used as stem cell sources due to faster engraftment and reduced risk of posttransplant infection. In this study, we demonstrated that a nucleotide sugar, UDP-glucose, which is released into extracellular fluids in response to stress, mediates HSPC mobilization. UDP-glucosemobilized cells possessed the capacity to achieve long-term repopulation in lethally irradiated animals and the ability to differentiate into multi-lineage blood cells. Compared with G-CSF-mobilized cells, UDP-glucose-mobilized cells preferentially supported long-term repopulation and exhibited lymphoid-biased differentiation, suggesting that UDP-glucose triggers the mobilization of functionally distinct subsets of HSPCs. Furthermore, co-administration of UDP-glucose and G-CSF led to greater HSPC mobilization than G-CSF alone. Administration of the antioxidant agent NAC significantly reduced UDP-glucose-induced mobilization, coinciding with a reduction in RANKL and osteoclastogenesis. These findings provide direct evidence demonstrating a potential role for UDP-glucose in HSPC mobilization and may provide an attractive strategy to improve the yield of stem cells in poor-mobilizing allogeneic or autologous donors.

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“…In the uterus, extracellular ATP is needed for the initiation and maintenance of myometrial contractions [3]; it contributes to the regulation of the uterine fluid microenvironment by regulating endometrial Cl − secretion [4], Na + absorption [5] and cervical mucus production [6]. P2X and P2Y nucleotide receptors have been identified in the female reproductive tract [7][8][9], with changes in the expression along the cycle [10] and during implantation [11] and pregnancy [8]. Furthermore, extracellular ATP treatment of sperm improves its fertilizing capability [12][13][14], thus potentially improving the outcome of assisted reproduction techniques.…”

Section: Introductionmentioning

confidence: 99%

Ecto-nucleotidases distribution in human cyclic and postmenopausic endometrium

Aliagas

Vidal

Torrejón‐Escribano

et al. 2012

Purinergic Signalling

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Extracellular ATP and its hydrolysis product, adenosine, acting through specific receptors collectively named purinergic receptors, regulate female fertility by influencing the endometrial fluid microenvironment. There are four major groups of ecto-nucleotidases that control the levels of extracellular ATP and adenosine and thus their availability at purinergic receptors: ecto-nucleoside triphosphate diphosphohydrolases (E-NTPDases), ecto-nucleotide pyrophosphatase/phospho-diesterases (E-NPPs), ecto-5′-nucleotidase (5′NT), and alkaline phosphatases (APs). The aim of the present work is to characterize the expression and distribution of ecto-nucleotidases in human endometrium along the menstrual cycle and after menopause, to evaluate their potential utility as fertility markers. We examined proliferative, secretory and atrophic endometria from women without endometrial pathology undergoing hysterectomy. We show that the ecto-nucleotidases are mainly present at endometrial epithelia, both luminal and glandular, and that their expression fluctuates along the cycle and also changes after menopause. An important result was identifying NPP3 as a new biological marker of tubal metaplasia. Our results emphasize the relevance of the study of purinergic signaling in human fertility.

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The UDP-Glucose Receptor P2RY14 Triggers Innate Mucosal Immunity in the Female Reproductive Tract by Inducing IL-8

Cited by 77 publications

References 55 publications

UDP-glucose promotes neutrophil recruitment in the lung

UDP-glucose promotes neutrophil recruitment in the lung

The nucleotide sugar UDP-glucose mobilizes long-term repopulating primitive hematopoietic cells

Ecto-nucleotidases distribution in human cyclic and postmenopausic endometrium

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